Movement Disorders

Vol. 23, No. 7, 2008, pp. 9981005

2008 Movement Disorder Society

Parkinsons Disease-Cognitive Rating Scale: A New

Cognitive Scale Specic for Parkinsons Disease
Javier Pagonabarraga, MD, Jaime Kulisevsky, MD, PhD,* Gisela Llebaria, MD,
Carmen Garca-Sanchez, MD, PhD, Berta Pascual-Sedano, MD, PhD, and Alexandre Gironell, MD, PhD
Movement Disorders Unit, Neurology Department, Sant Pau Hospital, Autonomous University of Barcelona,
and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain

Abstract: Cognitive defects associated with cortical pathology

may be a marker of dementia in Parkinsons disease (PD).
There is a need to improve the diagnostic criteria of PD dementia (PDD) and to clarify the cognitive impairment patterns
associated with PD. Current neuropsychological batteries
designed for PD are focused on fronto-subcortical decits but
are not sensitive for cortical dysfunction. We developed a new
scale, the Parkinsons Disease-Cognitive Rating Scale (PDCRS), that was designed to cover the full spectrum of cognitive defects associated with PD. We prospectively studied
92 PD patients [30 cognitively intact (CogInt), 30 mild cognitive impairment (MCI), 32 PDD] and 61 matched controls
who completed the PD-CRS and neuropsychological tests
assessing the cognitive domains included in the PD-CRS.
Acceptability, construct validity, reliability, and the discriminative properties of the PD-CRS were examined. The PD-CRS
included items assessing fronto-subcortical defects and items

assessing cortical dysfunction. Construct validity, test-retest

and inter-rater reliability of PD-CRS total scores showed an
intraclass correlation coefcient >0.70. The PD-CRS showed
an excellent test accuracy to diagnose PDD (sensitivity 94%,
specicity 94%). The PD-CRS total scores and confrontation
naming item scores-assessing cortical dysfunctionindependently differentiated PDD from non-demented PD. Alternating verbal uency and delayed verbal memory independently differentiated the MCI group from both controls and
CogInt. The PD-CRS appeared to be a reliable and valid PDspecic battery that accurately diagnosed PDD and detected
subtle fronto-subcortical decits. Performance on the PD-CRS
showed that PDD is characterized by the addition of cortical
dysfunction upon a predominant and progressive fronto-subcortical impairment.
2008 Movement Disorder Society
Key words: Parkinsons disease; cognition; dementia; rating scale; neuropsychological

Some degree of cognitive impairment is common in

nondemented Parkinsons disease patients (PD-ND) and
eventually progress to dementia in 24 to 31% of
patients.1 In population-based and cohort studies, from
23.5 to 55% of PD-ND patients show mild cognitive
defects since the early stages of the disease.24 The cognitive changes in PD are characterized by a frontal-subcortical impairment with decreased attention and executive function leading to progressive impairment in prefrontal tasks, visuospatial skills, and memory.2,5,6 Still,

20 to 25% of PD-ND patients may exhibit a pattern of

cortical impairment with memory tasks and confrontation naming defects,2 and cognitive ndings associated
with cortical pathology, such as language errors, develop in many patients with PD with dementia (PDD).7
Accordingly, neuroimaging and pathological studies
have variably correlated the development of PDD with
both frontal-subcortical and cortical alterations. Decreased fronto-striatal dopaminergic activity,8,9 widespread decrease of cortical cholinergic activity,10,11 and
higher cortical degeneration in the limbic/paralimbic
system have all been reported.1214 Thus, to capture the
whole spectrum of cognitive defects associated with PD,
neuropsychological evaluation should include items sensitive to cortical and frontal-subcortical dysfunction.
Only two published neuropsychological batteries
have been specically designed to target the most specic cognitive decits in PD.15,16 The Mini-Mental

This article contains supplementary material available via the Internet at http://www.interscience.wiley.com/jpages/0885-3185/suppmat.
*Correspondence to: Jaime Kulisevsky, Movement Disorders Unit,
Neurology Department, Sant Pau Hospital, Sant Antoni M, Claret
167, 08025 Barcelona, Spain. E-mail: jkulisevsky@santpau.es
Received 2 October 2007; Accepted 6 February 2008
Published online 31 March 2008 in Wiley InterScience (www.
interscience.wiley.com). DOI: 10.1002/mds.22007

998

COGNITIVE RATING SCALE FOR PD

Parkinson15 is a brief screening test aimed at identifying PD patients who require a more comprehensive
cognitive assessment. Only the pilot study was published, and the scale was not subjected to extensive
clinimetric evaluations.15 The SCOPA-COG is a short,
reliable and valid instrument sensitive to measure cognition in PD.16 However, the scale was constructed
with items assessing frontal-subcortical functions, but
did not include items sensitive to cortical dysfunction.
To address the need for a more comprehensive but
still practical tool for cognitive assessment we developed the Parkinsons Disease-Cognitive Rating Scale
(PD-CRS), a new PD-specic cognitive scale aiming to
capture the whole spectrum of cognitive functions
impaired over the course of PD. The information provided by the assessment of fronto-subcortical and cortical cognitive functions may help to increase the sensitivity and specicity to diagnose PDD, to separate subgroups of patients according to their pattern of
cognitive impairment since the early stages of the disease, and to detect those subjects with a higher risk to
eventually develop dementia.
PATIENTS AND METHODS
Subjects
Ninety-two patients with idiopathic PD fullling
diagnostic criteria for PD17 were prospectively
recruited from a sample of outpatients regularly attending the Movement Disorders Clinic at Sant Pau Hospital, Barcelona. Each patient was interviewed regarding
disease onset, education level, medication history and
current medications and dosage.18 PD patients were at
stable doses of medication the 4 weeks before inclusion and during the study.
Motor status and disease severity were assessed by
the Unied Parkinsons Disease rating scale (UPDRS)
and Hoehn and Yahr scale (H&Y).19 In accordance with
published research criteria, we used the 1-year rule to
distinguish between PDD and DLB.20,21 All experimental participants scored <4 on the Ischemia Score of
Hachinski et al.22 to rule out vascular dementia. To
screen for mood disorders, individuals with a cut-off
score 11 in the Hospital Anxiety and Depression Scale
(HADS)23 were excluded, as were those with abnormalities on brain CT or MRI in the past 12 months, abnormal blood tests or non-compensated systemic diseases,
or inability to read or understand Spanish.
Patients were classied as cognitively intact (CgInt),
PD with mild cognitive impairment (MCI) or PD with
dementia (PDD). Intact cognition was diagnosed when
patients had a score of 0 on the Clinical Dementia Rat-

999

ing Scale (CDR),24 MCI when the score was 0.5, and
PDD wshen the score was one and when they met
294.1 criteria for PDD on the Diagnostic and Statistical
Manual of Mental Disorders, revised Fourth Edition
(DSM IV-TR).25 Patients with motor uctuations were
examined during the on state.
Sixty-one age-, sex- and education-matched healthy
subjects, most of whom were spouses or caregivers of
the patients, served as the control group. None of the
controls had cognitive complaints or prior history of
cardiovascular risk factors or neurological or psychiatric illness.
Informed consent to participate in the study was
obtained from all patients or caregivers, as appropriate,
and from controls. The study was approved by the
Local Ethics Committee.
Procedure and Assessment of the Psychometric
Properties of the Scale
The PD-CRS items were selected to cover the full
spectrum of cognitive changes seen in PD. We divided
the items as either subcortical-type or corticaltype, depending on the neural correlates reported in
previous neuropsychological and neuroimaging studies.
Description and rationale for the selection of the PDCRS items included in the initial version of the scale
(content validity) is provided in E-Appendix 1.
The initial PD-CRS included 10 subcortical-type
items (attention, working memory, Stroop test, phonemic, semantic, alternating, and action verbal uencies,
immediate and delayed verbal memory, clock drawing),
and two cortical-type items (naming, copy of a clock).
Each patient was scheduled for four visits. At the rst
visit, a neurologist (JP) administered the Mattis Dementia Rating Scale (MDRS)26 and classied patients into
cognitive groups according to the CDR. A neuropsychologist (GL) blinded to the MDRS and CDR scores
administered a comprehensive neuropsychological battery with validated cognitive tasks that assessed the
same cognitive domains as those evaluated by the PDCRS. To assess concurrent validity and test-retest reliability, the same neuropsychologist (GL) administered
the PD-CRS at the second and third visits. Inter-rater
reliability was assessed by another neuropsychologist
(CG) at the fourth visit. The interval between rst and
second visits was 2 weeks and the interval between second, third and fourth visits was 6 6 2 weeks.
Concurrent validity was assessed with the following
comparisons: total PD-CRS scores with total MDRS
scores; attention and working memory with the digit
span forward and backward subtests of the WAIS-III27;
verbal uencies with the verbal uencies in the WAIS-

Movement Disorders, Vol. 23, No. 7, 2008

1000

J. PAGONABARRAGA ET AL.

III27; immediate and delayed verbal memory with the

Rey Auditory Verbal Learning Test28; naming with the
Boston Naming Test29; and drawing and copy of a clock
with the Judgement of Line Orientation Test (JLOT).30
Test-retest and inter-rater reliability were measured
for both total and individual item scores. Internal consistency was assessed with Cronbachs a. Intraclass
correlation coefcients31 were used to calculate concurrent validity and reliability analysis.
Acceptability was considered appropriate for each
PD-CRS item if there was <5% of missing values and
<15% of the respondents with the lowest and highest
possible scores (oor and ceiling effect).32
An initial discriminative validity analysis was carried out to determine the ability of the PD-CRS items
to differentiate between PD cognitive groups. One-way
ANOVA, the Kruskal-Wallis test, ANCOVA with age,
education, and the motor part of the UPDRS as covariates, and logistic regression analysis were used.
To design the nal version of the PD-CRS we
selected those items with an appropriate concurrent validity, reliability, and acceptability that showed the
best discriminative ability between cognitive groups.
Once the nal version of the PD-CRS was constructed,
we calculated the discriminative properties of the total,
subcortical and cortical PD-CRS scores, and the validity and reliability of PD-CRS and individual item
scores. Finally, ROC curves were constructed to assess
PD-CRS screening test accuracy for dementia in PD.
Signicance was set at P < 0.05 for all the analyses,
performed with the SPSS 13.0 statistical software.
RESULTS
Demographics
Ninety-two PD patients and 61 control subjects participated in the study. There were no signicant differences in age, education or gender between PD patients and
controls (Table 1). The study population consisted of
three cognitive groups: 30 CgInt patients (age 64.1 6 9
years, education 11.1 6 5 years); 30 patients with MCI
(age 70 6 7 years, education 9.6 6 5 years); and 32
patients with PDD (age 77.7 6 5 years, education 6.6 6
4 years). One-way ANOVA showed signicant differences between PD groups for both age [F(2, 89) 5 17.4;
P < 0.001] and education [F(2, 89) 5 6.4; P < 0.001].
Clinimetric Characteristics of the PD-CRS
Concurrent Validity
The intraclass correlation coefcient (ICC) of total
scores on the initial version of the PD-CRS showed a

Movement Disorders, Vol. 23, No. 7, 2008

TABLE 1. Demographic and clinical characteristics

of matched PD and CG
PD patients
(n 5 92)
Age (yr)
Education (yr)
Men (%)
MDRS
PD duration (yr)
Hoehn & Yahr (%)
1
2
3
4
5
UPDRS-III
Levodopa (mg/day)
DA-LED (mg/day)
Total LED (mg/day)

71.2 6 9.1
8.9 6 5.3
59.3%
123 6 17
8.2 6 5
8.8%
38.5%
39.6%
13.1%
0%
25.6 6 12
609.7 6 408
163.1 6 168
774.7 6 460

CG (n 5 61)

69 6 8.0
10.3 6 4
53.1%
138.3 6 2.9

0.13a
0.10a
0.49b
<0.0001a

Values are expressed as mean 6 SD, or percentage of subjects (%).

PD: Parkinsons disease; CG: Control Group; MDRS: Mattis dementia rating scale; UPDRS: Unied Parkinsons disease rating
scale; DA: Dopamine agonists; LED: levodopa equivalent dose.
a
T-tests for independent samples.
b 2
v test.

strong concurrent validity with the total score on the

MDRS (ICC 5 0.86). Strong concurrent validity was
also obtained for immediate (0.86) and delayed memory (0.85), alternating verbal uency (VF) (0.80),
action VF (0.86), phonemic VF (0.87), semantic VF
(0.85), attention (0.80), naming (0.71), and both drawing (0.71) and copy (0.73) of a clock. Scores on working memory showed a moderate concurrent validity
with digit span backward scores (0.64).
Reliability
The ICC of individual items, and total, cortical and
subcortical scores on the initial version of the PD-CRS
showed both a high test-retest and a high inter-rater
reliability.33 When evaluating test-retest reliability, the
ICC of individual items ranged from 0.84 to 0.91, and
the ICC of total, subcortical, and cortical scores were

0.90. Evaluation of the inter-rater reliability showed
the ICC of individual items to range from 0.77 to 0.88,
and that of the total, subcortical and cortical scores
were 0.93. The PD-CRS showed a high internal consistency (Cronbachs a 5 0.85). The corrected itemtotal correlations for the PD-CRS ranged from 0.73
(naming) to 0.87 (working memory). No item improved
Cronbachs a if removed.
Acceptability
The percentage of missing values was <5% for all
items. No oor effect or outliers were observed for any

COGNITIVE RATING SCALE FOR PD

1001

TABLE 2. Analysis of covariance (ANCOVA) between controls and PD cognitive groups (CgInt, MCI, and PDD), with age,
education, and UPDRS-III as covariates
Dependent Variable

Post-hoc analysis (signicant relationships)

Attention
Working memory
Phonemic uency
Semantic uency
Alternating uency
Action uency
Immediate verbal memory
Delayed verbal memory
Naming
Clock drawing
Copy of a clock

53.1
41.8
16.8
25.6
25.5
27.0
31.5
17.5
23.0
39.3
27.7

0.0004
0.0002
0.0001
0.0002
0.0002
0.0006
0.0001
0.0009
0.0003
0.0001
0.0003

MCI vs. controls

-Immediate memory (P 5 0.016) -Delayed memory (P < 0.001)
-Phonemic VF (P < 0.001) -Semantic VF (P 5 0.001)
-Alternating VF (P < 0.001) - Action VF (P < 0.001)
-Attention (P 5 0.001) -Working memory (P < 0.001)
Clock drawing (P 5 0.03)
MCI vs. CgInt
-Alternating VF (P 5 0.006)
-Working memory (P 5 0.04)
PDD vs. MCI
All subcortical-type items (P < 0.003)
-Naming (P 5 0.0007)
-Copy of a clock (P < 0.001)

PD: Parkinsons disease; CgInt: Cognitively intact; MCI: mild cognitive impairment; PDD: Parkinsons disease with dementia; PD-CRS: Parkinsons Disease-Cognitive Rating Scale; CDT: Clock Drawing Task.

cognitive item. When evaluating the PD group as a

whole, a ceiling effect (>15% of the respondents with
the highest possible score) was observed in naming
and the copy of a clock. However, this effect was
eliminated when we analyzed separately the PDD
group, in which no oor or ceiling effect was shown.
Therefore, none of the items was initially deleted.
Discriminative Validity
Univariate Analysis. Both the one-way ANOVA
and Kruskal-Wallis test analysis showed signicant differences between controls, CgInt, MCI, and PDD
groups for all the PD-CRS items (all P-values <
0.001). Since age, education, and the motor part of the
UPDRS [F(2, 89) 5 28.7; P < 0.001] were signicantly different between cognitive groups in the univariate analysis, we conducted an ANCOVA analysis
with age, education, and motor function as covariates.
Tests of between-subjects effects showed all the PDCRS items (P < 0.001) to be signicantly different
between cognitive groups (Table 2). In the post hoc
comparisons, working memory was the only item to
differentiate controls from CgInt, all the subcorticaltype items -but neither naming nor the copy of the
clock- differed MCI from controls, MCI differed from
the CgInt group by the alternating VF and working
memory, and both the cortical-type and subcorticaltype items differentiated PDD from MCI, CgInt and
controls (see Fig. 1). Thus, cortical-type item scores
were not signicantly different between the control,
CgInt and MCI groups, but selectively helped to differentiate PDD from each cognitive group. A post hoc

analysis considering only PD patients with mild dementia (CDR 5 1; n 5 10) also showed this group to score
signicantly lower than the MCI group in the two
cortical-type items [naming (P < 0.001), copy of the
clock (P 5 0.004)], and in action VF (P 5 0.01).
No evidence of heteroscedasticity was found when
examining the residuals for each cognitive item in the
scale.
Multivariate Analysis. Stepwise logistic regression
analysis (forward: conditional) showed that naming
(P 5 0.046; OR 5 0.18, CI95% 0.320.96), action VF
(P 5 0.034; OR 5 0.21, CI95% 0.050.89), and immediate memory (P 5 0.02; OR 5 0.06, CI 95% 0.01
0.36) independently differentiated PDD from the PDND group. The MCI group was independently differentiated from CgInt patients by the alternating VF (P 5
0.008; OR 5 0.79, CI 95% 0.660.94) and delayed
memory (P 5 0.04; OR 5 0.75, CI 95% 0.560.99).
Selection and Clinimetric Assessment of the Final
Version of the PD-CRS. For their greater ability to
discriminate between cognitive groups, alternating and
action verbal uencies were nally selected. The computerized version of the Stroop test did not displayed
appropriate discriminative properties, so that this item
was excluded from the nal version of the scale.
Total scores of the nal version of the PD-CRS
showed a strong concurrent validity with the total
MDRS scores (ICC 5 0.87, CI 95% 0.820.90). The
individual items, total, cortical and subcortical scores
of the nal version of the PD-CRS showed also a high
test-retest and a inter-rater reliability, with ICC ranging
from 0.75 to 0.94, as well as a high internal consistency (Cronbachs a 5 0.82).

Movement Disorders, Vol. 23, No. 7, 2008

1002

J. PAGONABARRAGA ET AL.

FIG. 1. Comparative progression

of impairment of subcorticaltype" (A, B) and cortical-type
(C,D) items in controls and PD
cognitive groups, showing an abrupt decrease in cortical-type
items scores in PDD. CG: control
group; MCI: mild cognitive impairment; PDD: Parkinsons disease with dementia.

One-way ANOVA and Kruskal-Wallis test analysis

showed signicant differences between controls, CgInt,
MCI, and PDD groups for total (P 5 0.0002;), cortical
(P 5 0.0001), and subcortical (P 5 0.0009) PD-CRS
scores (see Fig. 2). In the ANCOVA analysis, both
total and subcortical PD-CRS scores did not separate
controls from CgInt patients, but separated controls
and CgInt from MCI, and MCI from PDD patients.
PD-CRS cortical scores differentiated PDD from MCI
and CgInt, but did not differentiate MCI from controls
or CgInt patients. All these relationships had a signicance level of P < 0.01.
In the multivariate analysis, PDD were independently
differentiated from the PD-ND group by the PD-CRS
total score (P 5 0.0002; OR 5 0.79, CI95% 0.700.89).
Then, we used Receiver Operating Characteristic (ROC)
curve analysis to determine the optimal cutoff score for
the screening of dementia in our sample. ROC curve
showed that a cut-off score of 64 on the PD-CRS total
score yielded high sensitivity (94%) and specicity
(94%), and positive and negative predictive values (PPV
91%, NPV 96%). The area under the ROC curve was
0.98 (CI 95% 5 0.960.99). ROC curve analysis to discriminate MCI from CgInt patients yielded moderate
sensitivity and specicity for total PD-CRS scores (sensitivity 73%, specicity 84%) or subcortical PD-CRS
scores (sensitivity 77%, specicity 71%).

Movement Disorders, Vol. 23, No. 7, 2008

The overall duration of the nal version of the PDCRS was 16 6 3.6 min in the PD-ND group and 24 6
7.8 min in the PDD group. The content, instructions

FIG. 2. Comparison of PD-CRS total scores between cognitive

groups and controls (ANOVA, F[3, 149] 5 128.2; P 5 0.0002). *Post
hoc signicant differences from controls (P < 0.01). y Post hoc significant differences from CgInt (P < 0.01). Post hoc signicant differences from MCI (P < 0.01). The box plots show the median values
(center line of box), the 25th (lower line of box), 75th (upper line of
box), 10th (lower T bar), and 90th centiles (upper T bar) in each
group. Open circles (*) indicate mild outliers (1.53 interquartile
range). CG: Control Group; CogInt: Cognitively intact; MCI: mild
cognitive impairment; PDD: Parkinsons disease with dementia.

COGNITIVE RATING SCALE FOR PD

and scoring of the nal version of the PD-CRS are
provided in the E-Appendix 2.
DISCUSSION
The main results of our study show that the PDCRS: (1) is a valid, reliable and useful neuropsychological battery that accurately diagnoses PDD; (2)
detects mild fronto-subcortical decits in PD-ND
patients; and (3) shows that the transition from MCI to
PDD is characterized by the addition of corticaltype cognitive defects upon a progressive and predominant fronto-subcortical impairment.
The PD-CRS showed a strong concurrent validity
with the MDRS, a test of global cognitive function
that is specially useful in PD,34 and with cognitive
tasks widely accepted to assess each cognitive domain
included in our scale. This reects the ability of the
PD-CRS to measure the cognitive functions impaired
in PD. No oor effect was observed in any item of the
scale, which indicates that patients do not obtain minimum scores before severe cognitive impairment is
reached. When analyzing the PD group as a whole, a
ceiling effect was observed only in the cortical-type
items. This effect disappeared when the PDD group
was analyzed separately. This indicates the heterogeneous distribution of cortical-type item scores in our
sample, almost normal in the PD-ND group and
abruptly decreasing in the PDD group.
The discriminative analysis showed the ability of the
PD-CRS to detect the progressive decline in cognitive
function that is characteristic of PD.35 Total, cortical,
and subcortical PD-CRS scores, and items assessing
executive function presented a progressive impairment
within PD cognitive groups (see Fig. 2).
Particularly, MCI subjects differed from controls
only in the subcortical-type items, whereas the two
cortical-type items selectively appeared impaired in
the transition from MCI to PDD. Logistic regression
analysis showed the total PD-CRS score and naming to
independently differentiate PDD from PD-ND,
although cortical PD-CRS score did not differentiate
PDD from PD-ND. We acknowledge that PDD is a
predominantly attentional-executive dementia. Nevertheless, a cortical item such as naming independently
predicted the presence of dementia in our sample. This
reinforces the hypothesis that cognitive decline leading
to PDD is associated with the development of cognitive defects associated with cortical pathology,7 and
replicates results showing that PDD subjects have a
higher frequency of aphasic features than PD-ND individuals.36 On the other hand, in a recent community-

1003

based longitudinal study of newly diagnosed PD

patients, picture copying and semantic rather than phonemic verbal uency appeared as the most signicant
neuropsychological predictors of cognitive decline in
early PD-ND.37 The higher value of semantic verbal
uency in predicting cognitive decline suggests that a
breakdown in the semantic system, whose neural substrate is thought to lie within the temporal neocortex,
accounts for a higher risk of developing PDD.38 Naming is very sensitive to the integrity of the semantic
system and imposes fewer demands on effortful selfinitiated retrieval than semantic uency.38 Thus, if conrmed that PD-ND with cortical abnormalities represents a group at risk for PDD,37 using a scale with
cortical items could provide us with a useful predictive
instrument for dementia in PD.
Further, detection of cortical cognitive alterations
might help elucidate whether the coexistence of Alzheimer-type pathology in PD has a relevant impact on
the pattern and evolution of cognitive impairment in
PD.39
The nding that alternating VF independently differentiated MCI from CgInt patients replicates previous
results pointing towards this verbal uency as the most
sensitive task to detect mild cognitive defects in PDND.40 Consistent also with previous studies, action VF
appeared as an early indicator of the conversion from
PD-ND to PDD.41 Although clock-drawing tasks might
be confounded by PD motor symptoms, ANCOVA
analysis with motor function as a covariate still
showed clock-drawing to differentiate MCI from controls and the copy of a clock to differentiate PDD from
PD-ND patients.
We acknowledge some limitations of our study.
First, as we have not compared the PD-CRS with existing rating scales for cognitive dysfunction in PD, we
cannot demonstrate that a scale with subcortical and
cortical items performs better than a scale with subcortical items only. Second, the absence of a consensus
on the denition of mild cognitive impairment" in
PD42 led us to adopt MCI criteria used to classify subjects at risk for Alzheimers disease to categorize our
subjects as CgInt or MCI subjects. A more appropriate
denition of MCI specic for PD could improve the
discriminant ability of PD-CRS to screen for MCI in
PD.
Overall, our results show that the PD-CRS appears
to be a valid neuropsychological battery specic for
PD. It may prove useful in clinical research since it is
sensitive to mild fronto-subcortical decits, follows the
progressive impairment of executive function throughout the course of the disease, and includes cortical-

Movement Disorders, Vol. 23, No. 7, 2008

1004

J. PAGONABARRAGA ET AL.

type" cognitive tasks that may improve detection of

the transition from MCI to dementia. The discriminant
ability to diagnose dementia in PD shown by the PDCRS total score in the ROC analysis suggests that this
scale may also be a good instrument for screening purposes.
Future prospective studies could assess the ability of
the PD-CRS to detect patterns of cognitive impairment
with a distinct risk to develop dementia from the early
stages of the disease. Further investigation on the
transcultural validation of the PD-CRS, is also warranted.
Acknowledgments: (1) Work partially supported by public
research Grants from Fondo de Investigaciones Sanitarias
PI051916 and Centro de Investigaciones Biomedicas en RedEnfermedades Neurodegenerativas (CIBERNED), and from
La Fundacio La Marato de TV3, Expedient Number 060310.
(2) We thank the assistance and helpful comments given by
Dr. Christopher Goetz and Dr. Glenn Stebbins in writing this
manuscript. We also thank Ignasi Gich for his expert statistical advice.

REFERENCES
1. Aarsland D, Zaccai J, Brayne C. A systematic review of prevalence studies of dementia in Parkinsons disease. Mov Disord
2005;20:12551263.
2. Muslimovic D, Post B, Speelman JD, Schmand B. Cognitive prole of patients with newly diagnosed Parkinson disease. Neurology 2005;65:12391245.
3. Janvin C, Aarsland D, Larsen JP, Hugdahl K. Neuropsychological prole of patients with Parkinsons disease without dementia.
Dement Geriatr Cogn Disord 2003;15:126131.
4. Foltynie T, Brayne CE, Robbins TW, Barker RA. The cognitive
ability of an incident cohort of Parkinsons patients in the UK.
The CamPaIGN study. Brain 2004;127:550560.
5. Jacobs DM, Marder K, Cote LJ, Sano M, Stern Y, Mayeux R.
Neuropsychological characteristics of preclinical dementia in Parkinsons disease. Neurology 1995;45:16911696.
6. Ballard CG, Aarsland D, McKeith I, et al. Fluctuations in attention: PD dementia vs DLB with Parkinsonism. Neurology 2002;
59:17141720.
7. Galvin JE, Pollack J, Morris JC. Clinical phenotype of Parkinson
disease dementia. Neurology 2006;67:16051611.
8. Ito K, Nagano-Saito A, Kato T, et al. Striatal and extrastriatal
dysfunction in Parkinsons disease with dementia: a 6-[18F]uoro-L-dopa PET study. Brain 2002;125:13581365.
9. Lewis SJ, Dove A, Robbins TW, Barker RA, Owen AM. Cognitive impairments in early Parkinsons disease are accompanied
by reductions in activity in frontostriatal neural circuitry. J Neurosci 2003;23:63516356.
10. Hilker R, Thomas AV, Klein JC, et al. Dementia in Parkinson
disease: functional imaging of cholinergic and dopaminergic
pathways. Neurology 2005;65:17161722.
11. Dubois B, Pilon B, Lhermitte F, Agid Y. Cholinergic deciency
and frontal dysfunction in Parkinsons disease. Ann Neurol
1990;28:117121.
12. Burton EJ, McKeith IG, Burn DJ, Williams ED, OBrien JT.
Cerebral atrophy in Parkinsons disease with and without dementia: a comparison with Alzheimers disease, dementia with Lewy
bodies and controls. Brain 2004;127:791800.

Movement Disorders, Vol. 23, No. 7, 2008

13. Nagano-Saito A, Washimi Y, Arahata Y, et al. Cerebral atrophy

and its relation to cognitive impairment in Parkinson disease.
Neurology 2005;64:224229.
14. Beyer MK, Janvin CC, Larsen JP, Aarsland D. A magnetic resonance imaging study of patients with Parkinsons disease with
mild cognitive impairment and dementia using voxel-based
morphometry. J Neurol Neurosurg Psychiatry 2007;78:254
259.
15. Mahieux FMM, Boller F, Fermanian J, Guillard G. Mini-mental
Parkinson: rst validation study of a new bedside test constructed
for Parkinsons disease. Behav Neurol 1995;8:1522.
16. Marinus J, Visser M, Verwey NA, et al. Assessment of cognition
in Parkinsons disease. Neurology 2003;61:12221228.
17. Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical
diagnosis of idiopathic Parkinsons disease: a clinico-pathological
study of 100 cases. J Neurol Neurosurg Psychiatry 1992;55:181
184.
18. Grosset K, Needleman F, Macphee G, Grosset D. Switching
from ergot to nonergot dopamine agonists in Parkinsons disease:
a clinical series and ve-drug dose conversion table. Mov Disord
2004;19:13701374.
19. Hoehn MM, Yahr MD. Parkinsonism: onset, progression and
mortality. Neurology 1967;17:427442.
20. McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB
consortium. Neurology 2005;65:18631872.
21. Emre M, Aarsland D, Brown R, et al. Clinical diagnostic criteria
for dementia associated with Parkinsons disease. Mov Disord
2007;22:16891707.
22. Hachinski VC, Iliff LD, Zilhka E, et al. Cerebral blood ow in
dementia. Arch Neurol 1975;32:632637.
23. Marinus J, Leentjens AF, Visser M, Stiggelbout AM, van Hilten
JJ. Evaluation of the hospital anxiety and depression scale in
patients with Parkinsons disease. Clin Neuropharmacol 2002;25:
318324.
24. Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL. A
new clinical scale for the staging of dementia. Br J Psychiatry
1982;140:566572.
25. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed: DSM-IV. Washington, DC: APA
1994.
26. Schmidt R, Freidl W, Fazekas F, et al. The Mattis Dementia rating scale: normative data from 1,001 healthy volunteers. Neurology 1994;44:964966.
27. Wechsler D. Wechsler intelligence scale. San Antonio, TX: The
Psychological Corporation; 1997.
28. Schmidt M. Rey auditory and verbal learning test: a handbook.
Los Angeles, CA: Western Psychological Services; 1996.
29. Kaplan EFGH, Weintraub S. The boston naming test. Boston:
Kaplan and Goodglass; 1978.
30. Benton AL HK, deS Hamsher K, Varney NR, Spreen O. Contributions to neuropsychological assessment. New York: Oxford
University Press; 1983.
31. Landis JR, Koch GG. The measurement of observer agreement
for categorical data. Biometrics 1977;33:159174.
32. McHorney CA, Tarlov AR. Individual-patient monitoring in clinical practice: are available health status surveys adequate? Qual
Life Res 1995;4:293307.
33. Nunally. Psychometric theory, 2nd ed. New York, NY: McGrawHill; 1978.
34. Aarsland D, Litvan I, Salmon D, Galasko D, Wentzel-Larsen T,
Larsen JP. Performance on the dementia rating scale in Parkinsons disease with dementia and dementia with Lewy bodies:
comparison with progressive supranuclear palsy and Alzheimers disease. J Neurol Neurosurg Psychiatry 2003;74:1215
1220.
35. Aarsland D, Andersen K, Larsen JP, Lolk A, Nielsen H, KraghSorensen P. Risk of dementia in Parkinsons disease: a community-based, prospective study. Neurology 2001;56:730736.

COGNITIVE RATING SCALE FOR PD

36. Stern Y, Tang MX, Jacobs DM, et al. Prospective comparative
study of the evolution of probable Alzheimers disease and Parkinsons disease dementia. J Int Neuropsychol Soc 1998;4:279284.
37. Williams-Gray CH, Foltynie T, Brayne CE, Robbins TW, Barker
RA. Evolution of cognitive dysfunction in an incident Parkinsons disease cohort. Brain 2007;130:17871798.
38. Hodges JR, Patterson K. Is semantic memory consistently
impaired early in the course of Alzheimers disease? Neuroanatomical and diagnostic implications. Neuropsychologia 1995;33:
441459.

1005

39. Jellinger KA. The morphological basis of mental dysfunction in

Parkinsons disease. J Neurol Sci 2006;248:167172.
40. Zec RF, Landreth ES, Fritz S, et al. A comparison of phonemic,
semantic, and alternating word uency in Parkinsons disease.
Arch Clin Neuropsychol 1999;14:255264.
41. Piatt AL, Fields JA, Paolo AM, Koller WC, Troster AI. Lexical,
semantic, and action verbal uency in Parkinsons disease with
and without dementia. J Clin Exp Neuropsychol 1999;21:435443.
42. Dubois B. Is PD-MCI a useful concept? Mov Disord 2007;22:
12151216.

Movement Disorders, Vol. 23, No. 7, 2008

Content, instructions, and scoring of the final version of the Parkinsons

Disease Cognitive Rating Scale (PD-CRS)

Items are administered to the subjects in the same order as presented below.

1. Immediate free recall verbal memory.

Instruction: The subject is asked to read aloud the written words shown on 12
consecutive cards. Three trials are performed, and the subject is asked to recall as many
words as possible after each trial.
Content:

Words
LIGHT
SILK
SAND
EYELASH
RICE
TIE
BLACKBOARD
BICYCLE
STAR
LION
RING
FRAGRANCE

Score: 1 point for each word recalled. The highest number of words recalled in any one
trial is the score. (0-12)

2. Confrontation naming.
The subject is asked to name the line drawings shown on 20 consecutive cards. There is
no time limit for response, and only one trial is given. No semantic or phonemic cues are
provided. When objects are included in their context (bib, buckle, mane, hook, jingle bell,
and hoof), the examiner is allowed to indicate the part of the line drawing to be named.
Content:
Images (see line drawings at the end of
the appendix)
BIB
CANDLE
CHERRY
STOOL
ANCHOR
TURTLE
KITE
FISHBOWL
BULB
GUITAR
BUCKLE
MANE
HOOK
SCREWDRIVER

PANEL SCREEN
SAFETY PIN
JINGLE BELL
HOOF
EXTINGUISHER
DOOR BOLT

Score: 1 point for each line drawing correctly named. (0-20)

3. Sustained attention.
Instruction: An ascending series of letters and numbers are read to the subjects. The
subject is asked to report the number of letters in the sequence. Ten series of letters and
numbers are presented, divided into five levels of ascending complexity. Two training
series are provided at the beginning of the test.
Content:
Correct answer
2LT

2 letters

8A9

1 letter

2P654

1 letter

3A6KL

3 letters

B904LT

3 letters

3CP573

2 letters

Example

395L4ZA

3 letters

I1ASQ41

4 letters

75DA4TB2

4 letters

968437LC

2 letters

Z49ATD384

4 letters

95MD4SC3E

5 letters

Score: 1 point for each correct series. (0-10)

4. Working memory.
Instructions: The examiner reads aloud a randomized list of numbers and letters ranging
in length from 2 to 6 letters and numbers. After each series the subject is asked to repeat
the numbers first, and then the letters. This test ends when the subject is unable to give
the correct answer in two consecutive series. Two training series are provided at the
beginning of the test.
Content:
Correct answer
L2T

2LT

8A9

89A

M3

3M

7P

7P

G8M

8GM

Example

9I6

96I

T04A

04TA

7V6J

76VJ

M64NI

64MNI

35SGC

35SCG

1R9VB3

193RVB

M274Z9

2749MZ

Score: 1 point for each correct series. (0-10)

Clock drawing task.

Instructions:
5. Umprompted drawing of a clock: The subject is asked to draw a clock face on a
blank sheet of paper, and to set the hands at twenty-five minutes past ten. (0-10)
6. Copy drawing of a clock: The patient is asked to copy the presented clock. (0-10)

12
11

10

4
7

5
6

Unprompted

Copy

Yes

Yes No

No

The figure looks like a clock.

The clock is not divided by lines or sectors.
There is a symmetric disposition of numbers.
Only 1 to 12 numbers are drawn.
Hour numbers are correctly sequenced.
Only two hands are drawn.
Clock hands are represented as arrows.
Hour hand is shorter than minute hand.
No words have been written.
The number 25 has not been drawn.

Score: 1 point for each correct item. (0-10 for each task)

7. Delayed free recall verbal memory.

Instructions: The subject is asked to recall as many words as possible from the list of
words presented at the beginning of the scale.
Content:
Words
LIGHT
SILK
SAND
EYELASH
RICE

TIE
BLACKBOARD
BICYCLE
STAR
LION
RING
FRAGRANCE
Score: 1 point for each word recalled. (0-12)

8. Alternating verbal fluency.

Instructions: The subject is asked to alternately generate as many different words as
possible beginning with the letter S and words describing articles of clothing during 60
seconds. Participants are instructed not to use proper nouns or to repeat the same word
with a different ending (e.g., swim, swimming, swimsuit).
Score: 1 point for each correct answer maintaining the alternation between words
beginning with s and articles of clothing. (0-20)

9. Action verbal fluency.

Instructions: We used the instructions listed in Piatt et al. (reference number 45 in the
manuscript) for the action verbal fluency task. The instructions are as follows: During
60 seconds, Id like you to tell me as many different things as you can think of that
people do. I dont want you to use the same word with different endings, like eat, eating,
eaten. Also, just give me single words such as eat, or smell, rather than a sentence.
Score: 1 point for each correct answer. (0-30)

SCORES
ITEM

Points

1. Immediate free recall verbal memory

2. Confrontation naming
3. Sustained attention
4. Working memory
5. Umprompted drawing of a clock
6. Copy drawing of a clock
7. Delayed free recall verbal memory
8. Alternating verbal fluency
9. Action verbal fluency
SUBCORTICAL score (0-114)
CORTICAL score (0-20)
TOTAL score (0-134)

Subcortical and cortical PD-CRS scores were obtained by adding the raw scores of the
items within each group. Total scores on the PD-CRS were calculated by adding the
subcortical and cortical PD-CRS scores.

LINE DRAWINGS.
1. BIB

2. CANDLE

3. CHERRY

4. STOOL

5. ANCHOR

6. TURTLE

7. KITE

8. FISHBOWL

9. BULB

10. GUITAR

11. BUCKLE

12. MANE

13. HOOK

14. SCREWDRIVER

15. PANEL SCREEN

16. SAFETY PIN

17. JINGLE BELL

18. HOOF

19. EXTINGUISHER

20. DOOR BOLT

Description of the Parkinsons Disease-Cognitive Rating Scale (PDCRS)

1. Subcortical-type cognitive items:

- Attention/Executive functions: Disturbances in both the frontal regulation of
attentional processes and working memory occur early in PD-ND patients,1-3 and
progress throughout the course of the disease.4, 5 They both have been correlated with
prefrontal atrophy, dopaminergic hypometabolism in the dorsolateral prefrontal cortex
(DLPFC),6and underactivation of the caudate nucleus, the ventrolateral and the
DLPFC.7 Participants were asked to say how many letters were presented from among a
series of letters and numbers for assessing attention, and to recall separately a
randomized list of numbers and letters for assessing working memory.
- Resistance to interference: Susceptibility to interference is impaired in PD,8 but
discrepancies about the usefulness and early impairment of this cognitive function in
PD have been reported.2, 3 Resistance to interference relies also upon the DLPFC.9 The
test selected was a computerized version of the Stroop test.
- Verbal fluency (VF) and cognitive flexibility: Phonemic and semantic verbal
fluencies are progressively impaired over the course of the disease10, 11, and their
deterioration is indicative of PDD development. 10 Action verbal fluency (action VF)
appears to be an early indicator of the conversion from PD-ND to PDD.12 Alternating
verbal fluency (alternating VF) requires a mental shift to generate words belonging to
different categories, and is impaired since the earliest stages of the disease.13
Participants were asked to generate as many words as possible in 60 seconds for each
fluency task.

- Verbal memory: Free recall immediate and delayed verbal memory are markedly
impaired in PD-ND2, 14 and their deterioration is indicative of PDD development. 10, 15
Impairment in free recall memory appears to be more related to the defective use of
memory stores due to working memory deficits, than a reduced capacity of
storing/consolidating new information in the temporal lobes.16 The specific task selected
was to recall as many words as possible from a 12-word list.
- Visuoconstructional skills/Clock drawing: PD-ND and PDD17 are associated with
marked visuospatial deficits.17, 18 Visuoconstructional abilities depend on the
functionality of both the prefrontal cortex and the posterior visual cortical areas.19 The
specific task selected for this cognitive function was the unprompted drawing of a clock
set at twenty-five minutes past ten,
2. Cortical-type cognitive items:
- Confrontation naming: Naming is normal in PD-ND20, 21 but deteriorates in PDD.20,
21

The decline in naming in PDD is even more rapid than in AD.22 Naming has been

mainly correlated with cortical activity in the anteromedial and posteromedial temporal
cortex.23, 24 In this task, participants were asked to name 20 line drawings, with no time
constraint.
- Visuoperceptual skills/Copy of a clock: To assess the functionality of the posterior
visual cortical areas, we assessed the copy of a clock after the unprompted drawing of
such a clock, which has been shown to partially separate the frontal-subcortical from the
posterior cortical component of this cognitive function.25 The task selected was the copy
of a clock set at twenty-five minutes past ten.
The initial PD-CRS included 10 subcortical-type items (attention, working memory,
Stroop test, four verbal fluencies, immediate and delayed verbal memory, clock
drawing), and two cortical-type items (naming, copy of a clock). Total score ranged

from 0 to 204, subcortical score from 0 to 174, and cortical score from 0 to 30, with
higher scores indicating a better functioning.
1.
Gotham AM, Brown RG, Marsden CD. 'Frontal' cognitive function in patients with
Parkinson's disease 'on' and 'off' levodopa. Brain 1988;111:299-321.
2.
Muslimovic D, Post B, Speelman JD, Schmand B. Cognitive profile of patients with
newly diagnosed Parkinson disease. Neurology 2005;65:1239-1245.
3.
Janvin C, Aarsland D, Larsen JP, Hugdahl K. Neuropsychological profile of patients
with Parkinson's disease without dementia. Dement Geriatr Cogn Disord 2003;15:126-131.
4.
Ballard CG, Aarsland D, McKeith I, O'Brien J, Gray A, Cormack F, et al. Fluctuations
in attention: PD dementia vs DLB with parkinsonism. Neurology 2002;59:1714-1720.
5.
Owen AM, James M, Leigh PN, Summers BA, Marsden CD, Quinn NP, et al. Frontostriatal cognitive deficits at different stages of Parkinson's disease. Brain 1992;115:1727-1751.
6.
Bruck A, Aalto S, Nurmi E, Bergman J, Rinne JO. Cortical 6-[18F]fluoro-L-dopa
uptake and frontal cognitive functions in early Parkinson's disease. Neurobiol Aging
2005;26:891-898.
7.
Lewis SJ, Dove A, Robbins TW, Barker RA, Owen AM. Cognitive impairments in
early Parkinson's disease are accompanied by reductions in activity in frontostriatal neural
circuitry. J Neurosci 2003;23:6351-6356.
8.
Cools R, Barker RA, Sahakian BJ, Robbins TW. Mechanisms of cognitive set flexibility
in Parkinson's disease. Brain 2001;124:2503-2512.
9.
Peterson BS, Kane MJ, Alexander GM, Lacadie C, Skudlarski P, Leung HC, et al. An
event-related functional MRI study comparing interference effects in the Simon and Stroop
tasks. Brain Res Cogn Brain Res 2002;13:427-440.
10.
Jacobs DM, Marder K, Cote LJ, Sano M, Stern Y, Mayeux R. Neuropsychological
characteristics of preclinical dementia in Parkinson's disease. Neurology 1995;45:1691-1696.
11.
Henry JD, Crawford JR. Verbal fluency deficits in Parkinson's disease: a meta-analysis.
J Int Neuropsychol Soc 2004;10:608-622.
12.
Piatt AL, Fields JA, Paolo AM, Koller WC, Troster AI. Lexical, semantic, and action
verbal fluency in Parkinson's disease with and without dementia. J Clin Exp Neuropsychol
1999;21:435-443.
13.
Zec RF, Landreth ES, Fritz S, Grames E, Hasara A, Fraizer W, et al. A comparison of
phonemic, semantic, and alternating word fluency in Parkinson's disease. Arch Clin
Neuropsychol 1999;14:255-264.
14.
Ivory SJ, Knight RG, Longmore BE, Caradoc-Davies T. Verbal memory in nondemented patients with idiopathic Parkinson's disease. Neuropsychologia 1999;37:817-828.
15.
Hobson P, Meara J. Risk and incidence of dementia in a cohort of older subjects with
Parkinson's disease in the United Kingdom. Mov Disord 2004;19:1043-1049.
16.
Appollonio I, Grafman J, Clark K, Nichelli P, Zeffiro T, Hallett M. Implicit and explicit
memory in patients with Parkinson's disease with and without dementia. Arch Neurol
1994;51:359-367.
17.
Mosimann UP, Mather G, Wesnes KA, O'Brien JT, Burn DJ, McKeith IG. Visual
perception in Parkinson disease dementia and dementia with Lewy bodies. Neurology
2004;63:2091-2096.
18.
Huber SJ, Freidenberg DL, Shuttleworth EC, Paulson GW, Christy JA.
Neuropsychological impairments associated with severity of Parkinson's disease. J
Neuropsychiatry Clin Neurosci 1989;1:154-158.
19.
Lee TM, Liu HL, Hung KN, Pu J, Ng YB, Mak AK, et al. The cerebellum's
involvement in the judgment of spatial orientation: a functional magnetic resonance imaging
study. Neuropsychologia 2005;43:1870-1877.
20.
Aarsland D, Litvan I, Salmon D, Galasko D, Wentzel-Larsen T, Larsen JP. Performance
on the dementia rating scale in Parkinson's disease with dementia and dementia with Lewy
bodies: comparison with progressive supranuclear palsy and Alzheimer's disease. J Neurol
Neurosurg Psychiatry 2003;74:1215-1220.

21.
Frank EM, McDade HL, Scott WK. Naming in dementia secondary to Parkinson's,
Huntington's, and Alzheimer's diseases. J Commun Disord 1996;29:183-197.
22.
Stern Y, Tang MX, Jacobs DM, Sano M, Marder K, Bell K, et al. Prospective
comparative study of the evolution of probable Alzheimer's disease and Parkinson's disease
dementia. J Int Neuropsychol Soc 1998;4:279-284.
23.
Grossman M, McMillan C, Moore P, Ding L, Glosser G, Work M, et al. What's in a
name: voxel-based morphometric analyses of MRI and naming difficulty in Alzheimer's disease,
frontotemporal dementia and corticobasal degeneration. Brain 2004;127:628-649.
24.
Teipel SJ, Willoch F, Ishii K, Burger K, Drzezga A, Engel R, et al. Resting state
glucose utilization and the CERAD cognitive battery in patients with Alzheimer's disease.
Neurobiol Aging 2006;27:681-690.
25.
Royall DR, Cordes JA, Polk M. CLOX: an executive clock drawing task. J Neurol
Neurosurg Psychiatry 1998;64:588-594.